Oxytocin Dosing and Maternal-Fetal Effects Using a Pharmacokinetic Model

Abstract

Objective- Although oxytocin is widely used in labor and childbirth, questions remain regarding the pharmacokinetics (PK), pharmacodynamics (PD) and dose of oxytocin in pregnant people as well as the potential effects on the fetus and newborn. The objective of the current study was to use published studies to investigate the PK/PD and dose of oxytocin in pregnancy, examine the placental transfer of oxytocin through the development of a physiologically-based PK (PBPK) model, and postulate whether the model predicts the effect(s) of oxytocin on fetuses and newborn infants. Methods- A literature review of articles related to oxytocin in the areas of PK/PD, placental transfer and its influence on newborns were reviewed and summarized. A PBPK model for oxytocin was developed to predict maternal-fetal transfer. Results- Previous studies have demonstrated a positive relationship between the plasma oxytocin concentration and uterine contractions during labor. An ex vivo study demonstrated maternal to fetal and fetal to maternal oxytocin transfer, but a clinical study investigating oxytocin concentrations in umbilical blood could not confirm these results. Previous studies have suggested that a high concentration of oxytocin is related to fetal bradycardia and possibly autism in the child. Conclusion- The current study developed a PBPK model to measure the placental transfer of oxytocin and its potential for adverse effects on the fetus and developing child. Further research is needed to determine oxytocin’s efficacy and safety in the maternal population and in their fetuses and developing children, and modeling techniques such as PBPK will contribute to that understanding.